Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Zhang, Zhiwei; Cui, Zihan; Xie, Zailai; Li, Chang; Xu, Chun; Guo, Xia; Yu, Jie; Chen, Tengfei; Facchinetti, Francesco; Bohnenberger, Hanibal; Leong, Tracy L.; Xie, Yufeng; Mao, Xinliang; Zhao, Jun

doi:10.21037/tlcr-21-767

Cited by 31 publications

(22 citation statements)

References 56 publications

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“…Amplification or overexpression of TITF1 (thyroid transcription factor 1) on chromosome 14q13.3 can enhance lung cancer cell proliferation via inducing the expression of the ROR1 (receptor tyrosine kinase-like orphan receptor 1) [29] , [30] . Overexpression of CCND1 (Cyclin D1) promoted NSCLC proliferation and progression through regulating the cell cycle [31] . Finally, we examined subtype-specific DNA methylation-driven genes.…”

Section: Discussionmentioning

confidence: 99%

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

Weng

et al. 2022

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

Weng

et al. 2022

Computational and Structural Biotechnology Journal

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“…Emerging studies indicated that USP5, a unique member of DUBs that can speci cally recognize unanchored polyubiquitin, played an essential role in regulating the repair of DNA double-strand breaks [10], in ammatory responses [11], and stress responses [12]. Meanwhile, USP5 could regulate the stability of many tumorigenesis-associated proteins to in uence the progression of various cancers such as, hepatocellular carcinoma [17], pancreatic ductal adenocarcinoma [19,20], and non-small cell lung cancer (NSCLC) [14,15]. However, the signi cance of USP5 in pan-cancer has not been explored until now.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our results, USP5 had a certain diagnostic accuracy (AUC > 0.7) in 20 cancer types, especially in predicting BRCA, CHOL, DLBC, LGG, LUSC, PAAD and THYM (AUC > 0.9), indicating the potential clinical application value of USP5 as a reliable diagnostic biomarker. Meanwhile, as a unique member of DUBs, USP5 could regulate the stability of some key tumor-regulating molecular such as, HIF2α in BRCA [13], CyclinD1 in GBM [21], SLUG in LIHC [17], HDAC2 in OV [22], STAT3 [23], WT1 [20] and FOXM1 [24] in PAAD and β-catenin [25], PD-L1[26] and CCND1 [15] in NSCLC to promote cancer progression, and our ROC curve analysis showed the AUC of 0.905 in BRCA, 0.852 in GBM, 0.891 in LIHC, 0.820 in OV, 0.980 in PAAD and 0.946 in LUSC. Thus, the combination of USP5 with these tumor-related molecular separately may signi cantly improve the diagnostic accuracy for the above cancers.…”

Section: Discussionmentioning

confidence: 99%

“…As for the role of USP5 in cancer, it has attracted the attention from many researchers recently. The functional link between the aberrant USP5 expression and the development of various cancers such as breast cancer [13], lung cancer [14,15], colorectal cancer [16] and hepatocellular carcinoma [17] has been established by many studies. Meanwhile, USP5 has been demonstrated to be closely correlated with some key molecules and pathways regulating cancer, which indicates the potential value of USP5 as a novel treatment target for cancer [18].…”

Section: Introductionmentioning

confidence: 99%

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A pan-cancer analysis of USP5: its diagnostic, prognostic and immunological roles in human cancers

Yan

Guo

Deng

et al. 2023

Preprint

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Background Posttranslational modifications (PTM) of proteins, such as acetylation, deubiquitination, and phosphorylation play important roles in various kinds of cancer progression. Ubiquitin-specific proteinase 5 (USP5), a unique member of deubiquitinating enzymes (DUBs) which recognizes unanchored polyubiquitin specifically, could regulate the stability of many tumorigenesis-associated proteins to influence cancer initiation and progression. However, the diverse biological significance of USP5 in pan-cancer has not been systematically and comprehensively studied. Methods Here, we explored the role of USP5 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, and we also acquired and analyzed data via various software and web platforms such as R, GEPIA2.0, HPA, TISIDB, cBioPortal, UALCAN, TIMER 2.0, CancerSEA and BioGRID. Results USP5 expression was high in most cancers and differed significantly in different molecular and immune subtypes of cancers. In addition, USP5 had certain diagnostic value in multiple cancers, and high expression of USP5 generally predicted poor prognosis for cancer patients. We also found that the most frequent genetic alterations type of USP5 was mutation, and the DNA methylation level of USP5 decreased in various cancers. Furthermore, USP5 expression correlated with cancer-associated fibroblasts (CAFs), endothelial cells (EC) and genetic markers of immunodulators in cancers. Moreover, the result from single cell sequencing showed that USP5 could regulate several tumor biological behaviors such as apoptosis, DNA damage and metastasis. Gene enrichment analysis indicated “spliceosome” and “RNA splicing” may be the critical mechanism for USP5 to involve in cancer. Conclusion Taken together, our study elucidates the biological significance of USP5 in the diagnosis, prognosis and immune in human pan-cancer.

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“…Several studies have shown the effect of USP5 on NSCLC, including promoting the proliferation of NSCLC cells and stabilizing the expression of PD-L1 [ 12 , 13 ]. While in our study, we found that USP5 was highly expressed in NSCLC tissues and was associated with poor prognosis in patients.…”

Section: Introductionmentioning

confidence: 99%

EOAI, a ubiquitin-specific peptidase 5 inhibitor, prevents non-small cell lung cancer progression by inducing DNA damage

et al. 2023

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Objective Targeting deubiquitinases (DUBs) has emerged as a promising avenue for anticancer drug development. However, the effect and mechanism of pan-DUB inhibitor EOAI on non-small cell lung cancer (NSCLC) remains to be studied. Materials and methods The expression of ubiquitin-specific peptidase 5 (USP5) in NSCLC was evaluated by immunohistochemistry. The effect of the USP5 inhibitor, EOAI, on NSCLC cell growth and cell cycle was evaluated by CCK-8 and PI staining. Apoptosis was detected by Annexin V-FITC/PI double staining. Autophagy was examined by LC3 immunofluorescence. Comet assay and γ-H2AX immunofluorescence staining were used to detect DNA damage, and Western blotting was used to detect the expression of apoptosis, cycle, autophagy and DNA damage-related proteins. In vivo experiments demonstrated the effect of EOAI on NSCLC. Results We also found that USP5 was significantly upregulated in NSCLC tissues in this study. In addition, we show that EOAI can cause DNA damage in NSCLC cells while modulating the transcriptional activity of P53, thereby inducing cell cycle arrest in NSCLC cells, autophagy and apoptosis. In vivo experiments have shown that EOAI can inhibit tumors and synergistically enhance the anti-tumor effect of cisplatin. Conclusion USP5-mediated epigenetic regulation of oncogenes promotes the occurrence of NSCLC, which provides ideas for developing potential targeted therapy.

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Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Cited by 31 publications

References 56 publications

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

A pan-cancer analysis of USP5: its diagnostic, prognostic and immunological roles in human cancers

EOAI, a ubiquitin-specific peptidase 5 inhibitor, prevents non-small cell lung cancer progression by inducing DNA damage

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